PrPsc can be detected in buffy coat fractions of blood. Detection of PrPsc from buffy coat fractions provides a way to concentrate the sample and to remove interfering substances in plasma. However, the magnitude of detection is inversely related to the age of the blood sample at time of processing. That is, “aged” buffy coat samples retain less signal than matched buffy coat samples that are processed immediately. Therefore, sensitive and specific methods of detection of PrPsc in stored biological samples are needed in the art.